MXPA06000887A - Imidazo-pirimidinas y triazolo-pirimidinas: ligandos del receptor de benzodiazepina. - Google Patents

Info

Publication number

MXPA06000887A

MXPA06000887A MXPA06000887A MXPA06000887A MXPA06000887A MX PA06000887 A MXPA06000887 A MX PA06000887A MX PA06000887 A MXPA06000887 A MX PA06000887A MX PA06000887 A MXPA06000887 A MX PA06000887A MX PA06000887 A MXPA06000887 A MX PA06000887A

Authority

MX

Mexico

Prior art keywords

imidazol

triazolo

ylmethyl

propyl

pyridin

Prior art date

2003-07-25

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003446 ligand Substances 0.000 title abstract description 20
• 150000005237 imidazopyrimidines Chemical class 0.000 title description 4
• 102000004300 GABA-A Receptors Human genes 0.000 title description 2
• 108090000839 GABA-A Receptors Proteins 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 318
• 102000027484 GABAA receptors Human genes 0.000 claims abstract description 116
• 108091008681 GABAA receptors Proteins 0.000 claims abstract description 116
• 238000000034 method Methods 0.000 claims abstract description 60
• 230000027455 binding Effects 0.000 claims abstract description 55
• 230000000694 effects Effects 0.000 claims abstract description 46
• 102000005962 receptors Human genes 0.000 claims abstract description 45
• 108020003175 receptors Proteins 0.000 claims abstract description 45
• 238000011282 treatment Methods 0.000 claims abstract description 42
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
• -1 nitro, cyano, amino Chemical group 0.000 claims description 187
• 125000000217 alkyl group Chemical group 0.000 claims description 96
• 239000000203 mixture Substances 0.000 claims description 94
• 238000012360 testing method Methods 0.000 claims description 76
• 125000003545 alkoxy group Chemical group 0.000 claims description 70
• 229910052736 halogen Inorganic materials 0.000 claims description 63
• 125000001424 substituent group Chemical group 0.000 claims description 63
• 150000002367 halogens Chemical class 0.000 claims description 62
• 229910052739 hydrogen Inorganic materials 0.000 claims description 57
• 239000001257 hydrogen Substances 0.000 claims description 56
• 150000003839 salts Chemical class 0.000 claims description 53
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 49
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
• 150000002431 hydrogen Chemical class 0.000 claims description 39
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 35
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
• 125000001188 haloalkyl group Chemical group 0.000 claims description 33
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 31
• 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 30
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 239000000523 sample Substances 0.000 claims description 29
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 125000004076 pyridyl group Chemical group 0.000 claims description 25
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
• 208000019901 Anxiety disease Diseases 0.000 claims description 21
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 21
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 17
• 125000005518 carboxamido group Chemical group 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 17
• 208000019116 sleep disease Diseases 0.000 claims description 17
• 230000036506 anxiety Effects 0.000 claims description 16
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
• 125000001153 fluoro group Chemical group F* 0.000 claims description 13
• 239000012528 membrane Substances 0.000 claims description 13
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 11
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
• 150000005215 alkyl ethers Chemical class 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 10
• HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 claims description 9
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
• 125000001072 heteroaryl group Chemical group 0.000 claims description 9
• 208000020685 sleep-wake disease Diseases 0.000 claims description 9
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 8
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 8
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 8
• 230000006403 short-term memory Effects 0.000 claims description 8
• 230000019491 signal transduction Effects 0.000 claims description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims description 7
• 208000000044 Amnesia Diseases 0.000 claims description 7
• 206010012289 Dementia Diseases 0.000 claims description 7
• 230000007831 electrophysiology Effects 0.000 claims description 7
• 238000002001 electrophysiology Methods 0.000 claims description 7
• 125000000335 thiazolyl group Chemical group 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 238000005406 washing Methods 0.000 claims description 7
• 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 6
• UAMAIHOEGLEXSV-UHFFFAOYSA-N adipiplon Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F UAMAIHOEGLEXSV-UHFFFAOYSA-N 0.000 claims description 6
• 230000004075 alteration Effects 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• UWTLXBIEGTWTMZ-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine-2-carbonitrile Chemical compound N1=CN2C=C(C#N)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 UWTLXBIEGTWTMZ-UHFFFAOYSA-N 0.000 claims description 5
• 239000002253 acid Substances 0.000 claims description 5
• 238000000376 autoradiography Methods 0.000 claims description 5
• 239000000460 chlorine Substances 0.000 claims description 5
• 239000013068 control sample Substances 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• UYUZKXAGLYQINB-UHFFFAOYSA-N 2-[1-[(8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)methyl]imidazol-2-yl]pyridine-3-carbonitrile Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1C#N UYUZKXAGLYQINB-UHFFFAOYSA-N 0.000 claims description 4
• HRETYXMMIJBZRN-UHFFFAOYSA-N 6-[1-[(8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)methyl]imidazol-2-yl]pyridine-2-carbonitrile Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(C#N)=N1 HRETYXMMIJBZRN-UHFFFAOYSA-N 0.000 claims description 4
• IPXNSCRXLXHBIZ-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-methyl-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=C(C)N2C=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 IPXNSCRXLXHBIZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 4
• 102000005915 GABA Receptors Human genes 0.000 claims description 4
• 108010005551 GABA Receptors Proteins 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
• 230000002708 enhancing effect Effects 0.000 claims description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 230000001225 therapeutic effect Effects 0.000 claims description 4
• XQOLMNXEGDTGML-UHFFFAOYSA-N triazolo[1,5-c]pyrimidine Chemical compound C1=NC=CC2=CN=NN21 XQOLMNXEGDTGML-UHFFFAOYSA-N 0.000 claims description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
• BRFPCEPJPXZGDA-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-propan-2-yl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C(C)C)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F BRFPCEPJPXZGDA-UHFFFAOYSA-N 0.000 claims description 3
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 3
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 230000006735 deficit Effects 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
• 239000006188 syrup Substances 0.000 claims description 3
• 235000020357 syrup Nutrition 0.000 claims description 3
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 2
• CGUKQGIMXXFLSP-UHFFFAOYSA-N 3-ethyl-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=C(C)N2C(CC)=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 CGUKQGIMXXFLSP-UHFFFAOYSA-N 0.000 claims description 2
• VFIDEKLJABMLLR-UHFFFAOYSA-N 7-[[4-chloro-2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CCC)=C1CN1C=C(Cl)N=C1C1=NC=CC=C1F VFIDEKLJABMLLR-UHFFFAOYSA-N 0.000 claims description 2
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 2
• 229910014585 C2-Ce Inorganic materials 0.000 claims description 2
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 2
• USNPJDROMQCDAO-UHFFFAOYSA-N [7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl]methanol Chemical compound N1=CN2N=C(CO)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F USNPJDROMQCDAO-UHFFFAOYSA-N 0.000 claims description 2
• 239000002775 capsule Substances 0.000 claims description 2
• 230000003834 intracellular effect Effects 0.000 claims description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims 4
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 claims 3
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims 3
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 2
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 2
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
• NUJDBYIZEFSXJP-UHFFFAOYSA-N 1-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]propan-1-ol Chemical compound N1=CN2N=C(C)N=C2C(C(O)CC)=C1CN1C=CN=C1C1=NC=CC=C1F NUJDBYIZEFSXJP-UHFFFAOYSA-N 0.000 claims 1
• KDHJNMHGCNOHTL-UHFFFAOYSA-N 1-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl]ethanol Chemical compound N1=CN2N=C(C(C)O)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F KDHJNMHGCNOHTL-UHFFFAOYSA-N 0.000 claims 1
• CQIVCBJKDYNCEP-UHFFFAOYSA-N 1-[7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]propan-1-ol Chemical compound N1=CN2N=C(C)N=C2C(C(O)CC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 CQIVCBJKDYNCEP-UHFFFAOYSA-N 0.000 claims 1
• YMBCGEXQOACNHS-UHFFFAOYSA-N 2,8-diethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(CC)N=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C YMBCGEXQOACNHS-UHFFFAOYSA-N 0.000 claims 1
• GKYYCIFMTQMTHX-UHFFFAOYSA-N 2-(difluoromethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C(F)F)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F GKYYCIFMTQMTHX-UHFFFAOYSA-N 0.000 claims 1
• CQGORZBTKUXQKD-UHFFFAOYSA-N 2-[1-[(3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl)methyl]imidazol-2-yl]-1,3-thiazole Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CS1 CQGORZBTKUXQKD-UHFFFAOYSA-N 0.000 claims 1
• JCUWOVITNZXHFK-UHFFFAOYSA-N 2-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl]-1,3-thiazole Chemical compound N1=CN2N=C(C=3SC=CN=3)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F JCUWOVITNZXHFK-UHFFFAOYSA-N 0.000 claims 1
• MDMNLRIIJCLGPZ-UHFFFAOYSA-N 2-cyclobutyl-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C3CCC3)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 MDMNLRIIJCLGPZ-UHFFFAOYSA-N 0.000 claims 1
• NERZUYNHTDRKCC-UHFFFAOYSA-N 2-ethyl-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(CC)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F NERZUYNHTDRKCC-UHFFFAOYSA-N 0.000 claims 1
• PGVWGWOXXXTRBI-UHFFFAOYSA-N 2-ethyl-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=C(CC)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 PGVWGWOXXXTRBI-UHFFFAOYSA-N 0.000 claims 1
• OJGKSXCBHJNZDG-UHFFFAOYSA-N 2-methyl-8-propyl-7-[(2-pyridazin-3-ylimidazol-1-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CN=N1 OJGKSXCBHJNZDG-UHFFFAOYSA-N 0.000 claims 1
• MAMNCFUENSXJOF-UHFFFAOYSA-N 2-methyl-8-propyl-7-[(2-pyridin-2-ylimidazol-1-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC=N1 MAMNCFUENSXJOF-UHFFFAOYSA-N 0.000 claims 1
• VNRCPYKSCJJOCU-UHFFFAOYSA-N 3-(difluoromethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C(F)F)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F VNRCPYKSCJJOCU-UHFFFAOYSA-N 0.000 claims 1
• NZIZZDODSBLGRE-UHFFFAOYSA-N 3-cyclobutyl-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C3CCC3)=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 NZIZZDODSBLGRE-UHFFFAOYSA-N 0.000 claims 1
• ISHJJXZEBIOQIF-UHFFFAOYSA-N 3-methyl-8-propyl-7-[(2-pyridazin-3-ylimidazol-1-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CN=N1 ISHJJXZEBIOQIF-UHFFFAOYSA-N 0.000 claims 1
• UERUEYQWZYJQJC-UHFFFAOYSA-N 3-methyl-8-propyl-7-[(2-pyridin-2-ylimidazol-1-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC=N1 UERUEYQWZYJQJC-UHFFFAOYSA-N 0.000 claims 1
• FFLRKGVWGOSCAO-UHFFFAOYSA-N 6-[1-[(8-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl)methyl]imidazol-2-yl]-1h-pyridin-2-one Chemical compound N1=CN2C=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(O)=N1 FFLRKGVWGOSCAO-UHFFFAOYSA-N 0.000 claims 1
• XNCYXJSDXIITFC-UHFFFAOYSA-N 7-[[2-(2,5-difluorophenyl)imidazol-1-yl]methyl]-3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC(F)=CC=C1F XNCYXJSDXIITFC-UHFFFAOYSA-N 0.000 claims 1
• OEXYXFNMBFRMHW-UHFFFAOYSA-N 7-[[2-(2,5-difluorophenyl)imidazol-1-yl]methyl]-8-ethyl-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1F OEXYXFNMBFRMHW-UHFFFAOYSA-N 0.000 claims 1
• BXLMLBMXACCJJC-UHFFFAOYSA-N 7-[[2-(2,5-difluorophenyl)imidazol-1-yl]methyl]-8-ethyl-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1F BXLMLBMXACCJJC-UHFFFAOYSA-N 0.000 claims 1
• LBBRUTMMONIDJW-UHFFFAOYSA-N 7-[[2-(2,5-difluorophenyl)imidazol-1-yl]methyl]-8-ethyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1F LBBRUTMMONIDJW-UHFFFAOYSA-N 0.000 claims 1
• CEEJHZQYRZHFJU-UHFFFAOYSA-N 7-[[2-(2,6-difluorophenyl)imidazol-1-yl]methyl]-8-propyl-2-(trifluoromethyl)imidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=C(C(F)(F)F)N=C2C(CCC)=C1CN1C=CN=C1C1=C(F)C=CC=C1F CEEJHZQYRZHFJU-UHFFFAOYSA-N 0.000 claims 1
• ZYPLRHLOLLTGCF-UHFFFAOYSA-N 7-[[2-(2,6-difluorophenyl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CCC)=C1CN1C=CN=C1C1=C(F)C=CC=C1F ZYPLRHLOLLTGCF-UHFFFAOYSA-N 0.000 claims 1
• GFWPDWYNKPMUCK-UHFFFAOYSA-N 7-[[2-(2,6-difluorophenyl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=CN=C2C(CCC)=C1CN1C=CN=C1C1=C(F)C=CC=C1F GFWPDWYNKPMUCK-UHFFFAOYSA-N 0.000 claims 1
• ZYNLZENDPKIIDI-UHFFFAOYSA-N 7-[[2-(2-chlorophenyl)imidazol-1-yl]methyl]-8-ethyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC=C1Cl ZYNLZENDPKIIDI-UHFFFAOYSA-N 0.000 claims 1
• WINNWQRJCGNPKH-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-1-methyl-8-propylimidazo[1,5-c]pyrimidine Chemical compound N1=CN2C=NC(C)=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F WINNWQRJCGNPKH-UHFFFAOYSA-N 0.000 claims 1
• GZJOODXEUFJDCY-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-(methoxymethyl)-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(COC)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F GZJOODXEUFJDCY-UHFFFAOYSA-N 0.000 claims 1
• JTJGFFMMLFGUCS-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methoxy-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(OC)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F JTJGFFMMLFGUCS-UHFFFAOYSA-N 0.000 claims 1
• FFWKFXVAHOJBJD-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-8-(2-phenylmethoxyethyl)-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound C1=CN=C(C=2C(=CC=CN=2)F)N1CC=1N=CN2N=C(C)N=C2C=1CCOCC1=CC=CC=C1 FFWKFXVAHOJBJD-UHFFFAOYSA-N 0.000 claims 1
• ZEAWTFVUEKDYDK-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-phenyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C=3C=CC=CC=3)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F ZEAWTFVUEKDYDK-UHFFFAOYSA-N 0.000 claims 1
• DQSXIULXVLEYIP-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-propan-2-yloxy-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(OC(C)C)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F DQSXIULXVLEYIP-UHFFFAOYSA-N 0.000 claims 1
• SPIKZNVEROZJMT-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methoxy-5-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=C(C)N2C(OC)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F SPIKZNVEROZJMT-UHFFFAOYSA-N 0.000 claims 1
• DNRXICIPOQCKBX-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F DNRXICIPOQCKBX-UHFFFAOYSA-N 0.000 claims 1
• BSBGPAVQSMJLET-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-phenyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C=3C=CC=CC=3)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F BSBGPAVQSMJLET-UHFFFAOYSA-N 0.000 claims 1
• NBFWRPZRFCGSCI-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-propan-2-yl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C(C)C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F NBFWRPZRFCGSCI-UHFFFAOYSA-N 0.000 claims 1
• DCRXEJZBQJKWSR-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-(methoxymethyl)-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(COC)=C1CN1C=CN=C1C1=NC=CC=C1F DCRXEJZBQJKWSR-UHFFFAOYSA-N 0.000 claims 1
• ZSMOLXAKLVEJMX-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-(methoxymethyl)-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(COC)=C1CN1C=CN=C1C1=NC=CC=C1F ZSMOLXAKLVEJMX-UHFFFAOYSA-N 0.000 claims 1
• PNFBLOLXFIYSFD-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-2-(2,2,2-trifluoroethoxymethyl)-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(COCC(F)(F)F)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F PNFBLOLXFIYSFD-UHFFFAOYSA-N 0.000 claims 1
• TVWUSMPKIYMOFZ-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-2-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(CC(F)(F)F)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F TVWUSMPKIYMOFZ-UHFFFAOYSA-N 0.000 claims 1
• IJZQSEGBLMAYSB-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-2-pyrrolidin-1-yl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(N3CCCC3)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F IJZQSEGBLMAYSB-UHFFFAOYSA-N 0.000 claims 1
• YVNMREPZHJKGGJ-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C(F)(F)F)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F YVNMREPZHJKGGJ-UHFFFAOYSA-N 0.000 claims 1
• SIFVDHWCLQHABA-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-amine Chemical compound N1=CN2N=C(N)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F SIFVDHWCLQHABA-UHFFFAOYSA-N 0.000 claims 1
• DUCQNVVDVIJXFQ-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F DUCQNVVDVIJXFQ-UHFFFAOYSA-N 0.000 claims 1
• JUXFIJBURSYEMS-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine-2-carbonitrile Chemical compound N1=CN2N=C(C#N)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F JUXFIJBURSYEMS-UHFFFAOYSA-N 0.000 claims 1
• NLFNJZDYXHSTAE-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine-2-carboxamide Chemical compound N1=CN2N=C(C(N)=O)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F NLFNJZDYXHSTAE-UHFFFAOYSA-N 0.000 claims 1
• HMHIPFOQWVGGCP-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F HMHIPFOQWVGGCP-UHFFFAOYSA-N 0.000 claims 1
• SRRFWMVLLFIYMM-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=CN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F SRRFWMVLLFIYMM-UHFFFAOYSA-N 0.000 claims 1
• MSHZCEXGMYQMCX-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-n,n,8-tripropyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-amine Chemical compound N1=CN2N=C(N(CCC)CCC)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F MSHZCEXGMYQMCX-UHFFFAOYSA-N 0.000 claims 1
• VZJOLTPAOSKMGJ-UHFFFAOYSA-N 7-[[2-(5-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=C(F)C=N1 VZJOLTPAOSKMGJ-UHFFFAOYSA-N 0.000 claims 1
• JWGDOTNRVDLEMB-UHFFFAOYSA-N 7-[[2-(6-chloropyridin-2-yl)imidazol-1-yl]methyl]-8-ethyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC(Cl)=N1 JWGDOTNRVDLEMB-UHFFFAOYSA-N 0.000 claims 1
• CIAROHKHYKMXOX-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-1-methyl-8-propylimidazo[1,5-c]pyrimidine Chemical compound N1=CN2C=NC(C)=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 CIAROHKHYKMXOX-UHFFFAOYSA-N 0.000 claims 1
• UOFYVWZZEOSJGQ-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2,3-dimethyl-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=CN2C(C)=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 UOFYVWZZEOSJGQ-UHFFFAOYSA-N 0.000 claims 1
• ZSKRIUDQIWBRMG-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2,5-dimethyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=C(C)N2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 ZSKRIUDQIWBRMG-UHFFFAOYSA-N 0.000 claims 1
• RBLGHXBHKAXSQT-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-(methoxymethyl)-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(COC)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 RBLGHXBHKAXSQT-UHFFFAOYSA-N 0.000 claims 1
• UXWNKMOSBCUCQS-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-(methoxymethyl)-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(COC)=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 UXWNKMOSBCUCQS-UHFFFAOYSA-N 0.000 claims 1
• GPZBHPIUSIFZGF-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 GPZBHPIUSIFZGF-UHFFFAOYSA-N 0.000 claims 1
• CKJFUXWLEOSRIX-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-2-(trifluoromethyl)imidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=C(C(F)(F)F)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 CKJFUXWLEOSRIX-UHFFFAOYSA-N 0.000 claims 1
• OHTXUTOCHGSPJS-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 OHTXUTOCHGSPJS-UHFFFAOYSA-N 0.000 claims 1
• APMLNZIWQIIXOX-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 APMLNZIWQIIXOX-UHFFFAOYSA-N 0.000 claims 1
• JPOKMXYVDZDHCA-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine-3-carbonitrile Chemical compound N1=CN2C(C#N)=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 JPOKMXYVDZDHCA-UHFFFAOYSA-N 0.000 claims 1
• XZNLCOFEOPXPOV-UHFFFAOYSA-N 7-[[2-(6-methoxypyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(OC)=N1 XZNLCOFEOPXPOV-UHFFFAOYSA-N 0.000 claims 1
• ANCSYEJPAIWRPZ-UHFFFAOYSA-N 7-[[4-chloro-2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=C(Cl)N=C1C1=NC=CC=C1F ANCSYEJPAIWRPZ-UHFFFAOYSA-N 0.000 claims 1
• YXAVKYHITDRXEO-UHFFFAOYSA-N 8-(3-chloropropyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CCCCl)=C1CN1C=CN=C1C1=NC=CC=C1F YXAVKYHITDRXEO-UHFFFAOYSA-N 0.000 claims 1
• YBQFDTUPSVSURK-UHFFFAOYSA-N 8-(3-fluoropropyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CCCF)=C1CN1C=CN=C1C1=NC=CC=C1F YBQFDTUPSVSURK-UHFFFAOYSA-N 0.000 claims 1
• KNMRDOVCUPQPTJ-UHFFFAOYSA-N 8-(3-fluoropropyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CCCF)=C1CN1C=CN=C1C1=NC=CC=C1F KNMRDOVCUPQPTJ-UHFFFAOYSA-N 0.000 claims 1
• OQYSQSHFTRLINL-UHFFFAOYSA-N 8-ethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C OQYSQSHFTRLINL-UHFFFAOYSA-N 0.000 claims 1
• CPFQCLXQWTYQOL-UHFFFAOYSA-N 8-ethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C CPFQCLXQWTYQOL-UHFFFAOYSA-N 0.000 claims 1
• UJUIGMDOYZUWND-UHFFFAOYSA-N 8-ethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C UJUIGMDOYZUWND-UHFFFAOYSA-N 0.000 claims 1
• ATYJVOJHXYDRJD-UHFFFAOYSA-N 8-ethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C ATYJVOJHXYDRJD-UHFFFAOYSA-N 0.000 claims 1
• GBQVPQANRQCFKU-UHFFFAOYSA-N 8-ethyl-7-[[2-[3-(trifluoromethyl)phenyl]imidazol-1-yl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC(C(F)(F)F)=C1 GBQVPQANRQCFKU-UHFFFAOYSA-N 0.000 claims 1
• CAGUQAIBRHBQFA-UHFFFAOYSA-N 8-propyl-7-[(2-pyridin-2-ylimidazol-1-yl)methyl]-2-(trifluoromethyl)imidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=C(C(F)(F)F)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC=N1 CAGUQAIBRHBQFA-UHFFFAOYSA-N 0.000 claims 1
• YRURFFNAXDVJCE-UHFFFAOYSA-N 8-propyl-7-[(2-pyridin-2-ylimidazol-1-yl)methyl]imidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC=N1 YRURFFNAXDVJCE-UHFFFAOYSA-N 0.000 claims 1
• BJMVAFKNUUKUGJ-UHFFFAOYSA-N 8-propyl-7-[(2-thiophen-2-ylimidazol-1-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CS1 BJMVAFKNUUKUGJ-UHFFFAOYSA-N 0.000 claims 1
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
• SSKSDVCBYGGXSN-UHFFFAOYSA-N FC1=C(C=C(C=C1)F)C=1N(C=CN1)CC1=C(C=2N(C=N1)N=C(N2)C)CCC.C(CC)C=2C=1N(C=NC2CN2C(=NC=C2)C2=NC=CC=C2)N=CN1 Chemical compound FC1=C(C=C(C=C1)F)C=1N(C=CN1)CC1=C(C=2N(C=N1)N=C(N2)C)CCC.C(CC)C=2C=1N(C=NC2CN2C(=NC=C2)C2=NC=CC=C2)N=CN1 SSKSDVCBYGGXSN-UHFFFAOYSA-N 0.000 claims 1
• 208000026139 Memory disease Diseases 0.000 claims 1
• UTZOHNRHQJCAEQ-UHFFFAOYSA-N [7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-yl]methanol Chemical compound N1=CN2C(CO)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F UTZOHNRHQJCAEQ-UHFFFAOYSA-N 0.000 claims 1
• 239000000443 aerosol Substances 0.000 claims 1
• 150000007942 carboxylates Chemical group 0.000 claims 1
• 239000006071 cream Substances 0.000 claims 1
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
• XDSDDIXLTYRNFQ-UHFFFAOYSA-N ethyl 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine-3-carboxylate Chemical compound N1=CN2C(C(=O)OCC)=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 XDSDDIXLTYRNFQ-UHFFFAOYSA-N 0.000 claims 1
• 239000012530 fluid Substances 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 230000006984 memory degeneration Effects 0.000 claims 1
• 208000023060 memory loss Diseases 0.000 claims 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
• 239000006187 pill Substances 0.000 claims 1
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 60
• 210000003169 central nervous system Anatomy 0.000 abstract description 19
• 238000000338 in vitro Methods 0.000 abstract description 17
• 241001465754 Metazoa Species 0.000 abstract description 12
• 238000001727 in vivo Methods 0.000 abstract description 12
• 244000144972 livestock Species 0.000 abstract description 4
• 230000004807 localization Effects 0.000 abstract description 4
• 230000003389 potentiating effect Effects 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 115
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 239000002904 solvent Substances 0.000 description 65
• 235000019439 ethyl acetate Nutrition 0.000 description 50
• 239000000243 solution Substances 0.000 description 49
• 210000004027 cell Anatomy 0.000 description 44
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
• 239000010410 layer Substances 0.000 description 38
• 239000007787 solid Substances 0.000 description 31
• 238000006243 chemical reaction Methods 0.000 description 30
• 239000000047 product Substances 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• 239000000556 agonist Substances 0.000 description 26
• 239000012044 organic layer Substances 0.000 description 25
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
• 239000012267 brine Substances 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 22
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
• 229940049706 benzodiazepine Drugs 0.000 description 19
• 230000015572 biosynthetic process Effects 0.000 description 19
• 239000000284 extract Substances 0.000 description 18
• 238000003786 synthesis reaction Methods 0.000 description 18
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 16
• 241000700159 Rattus Species 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• 208000015114 central nervous system disease Diseases 0.000 description 15
• 229940079593 drug Drugs 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 15
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
• 239000011734 sodium Substances 0.000 description 14
• 125000002252 acyl group Chemical group 0.000 description 13
• 125000003118 aryl group Chemical group 0.000 description 13
• 239000012043 crude product Substances 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• 101150041968 CDC13 gene Proteins 0.000 description 12
• 229910052799 carbon Inorganic materials 0.000 description 12
• 208000035475 disorder Diseases 0.000 description 12
• 210000001519 tissue Anatomy 0.000 description 12
• 238000005481 NMR spectroscopy Methods 0.000 description 11
• 125000004429 atom Chemical group 0.000 description 11
• 208000010877 cognitive disease Diseases 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• 238000000746 purification Methods 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
• 229910000027 potassium carbonate Inorganic materials 0.000 description 9
• 150000003230 pyrimidines Chemical class 0.000 description 9
• 235000017557 sodium bicarbonate Nutrition 0.000 description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
• 229940126162 GABAA receptor modulator Drugs 0.000 description 8
• 241000282412 Homo Species 0.000 description 8
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 230000008859 change Effects 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 150000002148 esters Chemical class 0.000 description 8
• 238000009472 formulation Methods 0.000 description 8
• 239000008187 granular material Substances 0.000 description 8
• 238000011534 incubation Methods 0.000 description 8
• 210000004185 liver Anatomy 0.000 description 8
• 238000000926 separation method Methods 0.000 description 8
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
• 230000009471 action Effects 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• 235000015320 potassium carbonate Nutrition 0.000 description 7
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
• XUFCBCHWTOAVAA-UHFFFAOYSA-N [1,2,4]triazolo[4,3-c]pyrimidine Chemical class C1=CN=CN2C=NN=C21 XUFCBCHWTOAVAA-UHFFFAOYSA-N 0.000 description 6
• 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
• 235000014113 dietary fatty acids Nutrition 0.000 description 6
• 229940088598 enzyme Drugs 0.000 description 6
• 239000000194 fatty acid Substances 0.000 description 6
• 229930195729 fatty acid Natural products 0.000 description 6
• 150000004665 fatty acids Chemical class 0.000 description 6
• 239000000796 flavoring agent Substances 0.000 description 6
• 125000000623 heterocyclic group Chemical group 0.000 description 6
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 125000004043 oxo group Chemical group O=* 0.000 description 6
• 230000000144 pharmacologic effect Effects 0.000 description 6
• 239000003755 preservative agent Substances 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 229910052722 tritium Inorganic materials 0.000 description 6
• 208000020925 Bipolar disease Diseases 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
• 229910004373 HOAc Inorganic materials 0.000 description 5
• 239000007983 Tris buffer Substances 0.000 description 5
• QLOWGDIISXJREF-UHFFFAOYSA-N [1,2,4]triazolo[1,5-c]pyrimidine Chemical class C1=CN=CN2N=CN=C21 QLOWGDIISXJREF-UHFFFAOYSA-N 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 238000004440 column chromatography Methods 0.000 description 5
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 5
• 230000007423 decrease Effects 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 235000013355 food flavoring agent Nutrition 0.000 description 5
• 235000003599 food sweetener Nutrition 0.000 description 5
• 125000005842 heteroatom Chemical group 0.000 description 5
• 239000003999 initiator Substances 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 239000002464 receptor antagonist Substances 0.000 description 5
• 201000000980 schizophrenia Diseases 0.000 description 5
• 210000002966 serum Anatomy 0.000 description 5
• 238000010561 standard procedure Methods 0.000 description 5
• 238000004809 thin layer chromatography Methods 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
• WWQZBUAMHSXHAK-UHFFFAOYSA-N 4-chloro-6-methyl-5-(2-phenylmethoxyethyl)pyrimidine Chemical compound CC1=NC=NC(Cl)=C1CCOCC1=CC=CC=C1 WWQZBUAMHSXHAK-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 241000282472 Canis lupus familiaris Species 0.000 description 4
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• 239000007900 aqueous suspension Substances 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 230000000747 cardiac effect Effects 0.000 description 4
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 239000007859 condensation product Substances 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 238000001035 drying Methods 0.000 description 4
• 206010015037 epilepsy Diseases 0.000 description 4
• 235000019441 ethanol Nutrition 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 229960004381 flumazenil Drugs 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 150000002429 hydrazines Chemical class 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• 239000002480 mineral oil Substances 0.000 description 4
• 235000010446 mineral oil Nutrition 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• 210000000287 oocyte Anatomy 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 230000036961 partial effect Effects 0.000 description 4
• 229940044551 receptor antagonist Drugs 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 238000007363 ring formation reaction Methods 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 4
• 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 4
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 3
• 238000005160 1H NMR spectroscopy Methods 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• BREBLOQLDAMOQJ-UHFFFAOYSA-N 4-(bromomethyl)-6-chloropyrimidine Chemical compound ClC1=CC(CBr)=NC=N1 BREBLOQLDAMOQJ-UHFFFAOYSA-N 0.000 description 3
• YQYRMALXDGWNIE-UHFFFAOYSA-N 4-chloro-6-(chloromethyl)-2-methyl-5-propylpyrimidine Chemical compound CCCC1=C(Cl)N=C(C)N=C1CCl YQYRMALXDGWNIE-UHFFFAOYSA-N 0.000 description 3
• FIPOFHABVOQICE-UHFFFAOYSA-N 4-chloro-6-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-5-propylpyrimidine Chemical compound CCCC1=C(Cl)N=C(C)N=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 FIPOFHABVOQICE-UHFFFAOYSA-N 0.000 description 3
• 230000002407 ATP formation Effects 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 208000008811 Agoraphobia Diseases 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 208000028698 Cognitive impairment Diseases 0.000 description 3
• CJBBDLBWIJEQDS-UHFFFAOYSA-N FC=1C(=NC=CC1)C=1N(C=CN1)CC1=NC=C(C=2N1N=C(N2)N2CCCC2)CCC Chemical compound FC=1C(=NC=CC1)C=1N(C=CN1)CC1=NC=C(C=2N1N=C(N2)N2CCCC2)CCC CJBBDLBWIJEQDS-UHFFFAOYSA-N 0.000 description 3
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
• 208000018737 Parkinson disease Diseases 0.000 description 3
• 235000019483 Peanut oil Nutrition 0.000 description 3
• 206010034912 Phobia Diseases 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 241000283984 Rodentia Species 0.000 description 3
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
• 208000013200 Stress disease Diseases 0.000 description 3
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
• 229930006000 Sucrose Natural products 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 239000006096 absorbing agent Substances 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 208000012826 adjustment disease Diseases 0.000 description 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 235000011114 ammonium hydroxide Nutrition 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• 230000000949 anxiolytic effect Effects 0.000 description 3
• 229910052786 argon Inorganic materials 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 239000011575 calcium Substances 0.000 description 3
• 239000004202 carbamide Substances 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 238000009833 condensation Methods 0.000 description 3
• 230000005494 condensation Effects 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 230000001054 cortical effect Effects 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• FQQZGZZZSPUFKV-UHFFFAOYSA-N diethyl 2-oxo-3-propylbutanedioate Chemical compound CCOC(=O)C(CCC)C(=O)C(=O)OCC FQQZGZZZSPUFKV-UHFFFAOYSA-N 0.000 description 3
• 238000006073 displacement reaction Methods 0.000 description 3
• 238000009826 distribution Methods 0.000 description 3
• 239000003651 drinking water Substances 0.000 description 3
• 235000020188 drinking water Nutrition 0.000 description 3
• 208000024732 dysthymic disease Diseases 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• VPFQMRIZDITMRF-UHFFFAOYSA-N ethyl 6-chloro-2-methyl-5-propylpyrimidine-4-carboxylate Chemical compound CCCC1=C(Cl)N=C(C)N=C1C(=O)OCC VPFQMRIZDITMRF-UHFFFAOYSA-N 0.000 description 3
• 125000004494 ethyl ester group Chemical group 0.000 description 3
• OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 3
• AGYYYBIAZFILKT-UHFFFAOYSA-N imidazo[1,5-c]pyrimidine Chemical class C1=NC=CC2=CN=CN21 AGYYYBIAZFILKT-UHFFFAOYSA-N 0.000 description 3
• 238000002513 implantation Methods 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• OUZHSICGLODTRD-UHFFFAOYSA-N methyl 3-oxo-2-(2-phenylmethoxyethyl)butanoate Chemical compound COC(=O)C(C(C)=O)CCOCC1=CC=CC=C1 OUZHSICGLODTRD-UHFFFAOYSA-N 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 208000019906 panic disease Diseases 0.000 description 3
• 239000000312 peanut oil Substances 0.000 description 3
• 208000028173 post-traumatic stress disease Diseases 0.000 description 3
• 230000002035 prolonged effect Effects 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 208000020016 psychiatric disease Diseases 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 239000011541 reaction mixture Substances 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• 230000035939 shock Effects 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 238000001308 synthesis method Methods 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 235000015112 vegetable and seed oil Nutrition 0.000 description 3
• 239000008158 vegetable oil Substances 0.000 description 3
• 239000003643 water by type Substances 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
• CLFNVGKTQZMJOZ-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)pyridine-3-carbonitrile Chemical compound N#CC1=CC=CN=C1C1=NC=CN1 CLFNVGKTQZMJOZ-UHFFFAOYSA-N 0.000 description 2
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
• PQNVFSJRSGPRCQ-UHFFFAOYSA-N 2-[4-(bromomethyl)-6-chloropyrimidin-5-yl]ethyl acetate Chemical compound CC(=O)OCCC1=C(Cl)N=CN=C1CBr PQNVFSJRSGPRCQ-UHFFFAOYSA-N 0.000 description 2
• BMWSWAZIPWQQQY-UHFFFAOYSA-N 2-chloro-6-(1h-imidazol-2-yl)pyridine Chemical compound ClC1=CC=CC(C=2NC=CN=2)=N1 BMWSWAZIPWQQQY-UHFFFAOYSA-N 0.000 description 2
• QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 2
• RITANUMAGKGDNG-UHFFFAOYSA-N 2-fluoro-6-(1h-imidazol-2-yl)pyridine Chemical compound FC1=CC=CC(C=2NC=CN=2)=N1 RITANUMAGKGDNG-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
• BFKYQYMHJANOTR-UHFFFAOYSA-N 2h-pyrimidine-1-carbonitrile Chemical compound N#CN1CN=CC=C1 BFKYQYMHJANOTR-UHFFFAOYSA-N 0.000 description 2
• OZIMPUNGBUYCSP-UHFFFAOYSA-N 3-fluoropyridine-2-carbaldehyde Chemical compound FC1=CC=CN=C1C=O OZIMPUNGBUYCSP-UHFFFAOYSA-N 0.000 description 2
• GMDGYAWRTKWQNF-UHFFFAOYSA-N 4-(bromomethyl)-6-chloro-5-(2-phenylmethoxyethyl)pyrimidine Chemical compound ClC1=NC=NC(CBr)=C1CCOCC1=CC=CC=C1 GMDGYAWRTKWQNF-UHFFFAOYSA-N 0.000 description 2
• BSHDFQNEAUTALT-UHFFFAOYSA-N 4-azido-6-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-5-propylpyrimidine Chemical compound N1=C(C)N=C(N=[N+]=[N-])C(CCC)=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 BSHDFQNEAUTALT-UHFFFAOYSA-N 0.000 description 2
• FCNRSNSKMCLLPT-UHFFFAOYSA-N 6-(1h-imidazol-2-yl)pyridine-2-carbonitrile Chemical compound N#CC1=CC=CC(C=2NC=CN=2)=N1 FCNRSNSKMCLLPT-UHFFFAOYSA-N 0.000 description 2
• XFXGHXOOVFSOMW-UHFFFAOYSA-N 6-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-propylpyrimidin-4-amine Chemical compound CCCC1=C(N)N=CN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 XFXGHXOOVFSOMW-UHFFFAOYSA-N 0.000 description 2
• OTRUOKFWHWEOHQ-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-3h-[1,2,4]triazolo[1,5-c]pyrimidin-2-one Chemical compound N1=CN2N=C(O)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F OTRUOKFWHWEOHQ-UHFFFAOYSA-N 0.000 description 2
• AFVWKPXVQGAVPE-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 AFVWKPXVQGAVPE-UHFFFAOYSA-N 0.000 description 2
• HPHGNNAKSJAQKR-UHFFFAOYSA-N 7-methyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound CCCC1=C(C)N=CN2N=CN=C12 HPHGNNAKSJAQKR-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• CDFFJLUXSUAEDN-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CC(F)F)=C1CN1C=CN=C1C1=NC=CC=C1F CDFFJLUXSUAEDN-UHFFFAOYSA-N 0.000 description 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
• 208000030507 AIDS Diseases 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 208000007848 Alcoholism Diseases 0.000 description 2
• 208000031091 Amnestic disease Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 108010017384 Blood Proteins Proteins 0.000 description 2
• 102000004506 Blood Proteins Human genes 0.000 description 2
• 108091006146 Channels Proteins 0.000 description 2
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 2
• 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 2
• 102100038018 Corticotropin-releasing factor receptor 1 Human genes 0.000 description 2
• 208000020401 Depressive disease Diseases 0.000 description 2
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
• 201000010374 Down Syndrome Diseases 0.000 description 2
• XTYNYYWJZZOUED-UHFFFAOYSA-N FC=1C(=NC=CC1)C=1N(C=CN1)CC1=NC=C(C=2N1N=C(N2)N)CCC Chemical compound FC=1C(=NC=CC1)C=1N(C=CN1)CC1=NC=C(C=2N1N=C(N2)N)CCC XTYNYYWJZZOUED-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 208000011688 Generalised anxiety disease Diseases 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 102000009493 Neurokinin receptors Human genes 0.000 description 2
• 108050000302 Neurokinin receptors Proteins 0.000 description 2
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
• 208000006199 Parasomnias Diseases 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 208000028017 Psychotic disease Diseases 0.000 description 2
• 208000000810 Separation Anxiety Diseases 0.000 description 2
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 2
• 208000030886 Traumatic Brain injury Diseases 0.000 description 2
• KCTUDVHFDFICHN-UHFFFAOYSA-N [6-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-propylpyrimidin-4-yl]hydrazine Chemical compound N1=CN=C(NN)C(CCC)=C1CN1C(C=2C(=CC=CN=2)F)=NC=C1 KCTUDVHFDFICHN-UHFFFAOYSA-N 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 230000007000 age related cognitive decline Effects 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 125000000278 alkyl amino alkyl group Chemical group 0.000 description 2
• 125000005011 alkyl ether group Chemical group 0.000 description 2
• 230000003281 allosteric effect Effects 0.000 description 2
• 150000001409 amidines Chemical class 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 230000006986 amnesia Effects 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 239000003420 antiserotonin agent Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 208000025748 atypical depressive disease Diseases 0.000 description 2
• 230000004888 barrier function Effects 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 239000000544 cholinesterase inhibitor Substances 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000006999 cognitive decline Effects 0.000 description 2
• 230000001149 cognitive effect Effects 0.000 description 2
• 210000004748 cultured cell Anatomy 0.000 description 2
• 208000026725 cyclothymic disease Diseases 0.000 description 2
• 230000000994 depressogenic effect Effects 0.000 description 2
• 229910052805 deuterium Inorganic materials 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 206010013663 drug dependence Diseases 0.000 description 2
• YTBCMXDUUWYQML-UHFFFAOYSA-N ethyl 2-methyl-4-oxo-5-propyl-1h-pyrimidine-6-carboxylate Chemical compound CCCC1=C(O)N=C(C)N=C1C(=O)OCC YTBCMXDUUWYQML-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000000763 evoking effect Effects 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 208000029364 generalized anxiety disease Diseases 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 210000003494 hepatocyte Anatomy 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 229940053999 hypnotics and sedatives melatonin receptor agonists Drugs 0.000 description 2
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 206010022437 insomnia Diseases 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 125000000468 ketone group Chemical group 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
• 238000004020 luminiscence type Methods 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 108020004999 messenger RNA Proteins 0.000 description 2
• 230000003228 microsomal effect Effects 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 239000000472 muscarinic agonist Substances 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 239000000181 nicotinic agonist Substances 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 230000009871 nonspecific binding Effects 0.000 description 2
• 150000002894 organic compounds Chemical class 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 230000002611 ovarian Effects 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 125000002071 phenylalkoxy group Chemical group 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 238000000159 protein binding assay Methods 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 239000002287 radioligand Substances 0.000 description 2
• 230000008707 rearrangement Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 239000000932 sedative agent Substances 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 239000000952 serotonin receptor agonist Substances 0.000 description 2
• 238000004088 simulation Methods 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 230000002557 soporific effect Effects 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 201000001716 specific phobia Diseases 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 208000011117 substance-related disease Diseases 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 230000009529 traumatic brain injury Effects 0.000 description 2
• PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 230000002618 waking effect Effects 0.000 description 2
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• IYXUFOCLMOXQSL-UHFFFAOYSA-N (2,2-difluoroacetyl) 2,2-difluoroacetate Chemical compound FC(F)C(=O)OC(=O)C(F)F IYXUFOCLMOXQSL-UHFFFAOYSA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• 125000006729 (C2-C5) alkenyl group Chemical group 0.000 description 1
• 125000006730 (C2-C5) alkynyl group Chemical group 0.000 description 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• GEYSGGMNQZJFIL-UHFFFAOYSA-N 2-(bromomethyl)pyrimidine Chemical compound BrCC1=NC=CC=N1 GEYSGGMNQZJFIL-UHFFFAOYSA-N 0.000 description 1
• MSFVEEFXECBJPG-UHFFFAOYSA-N 2-(chloromethyl)pyrimidine Chemical compound ClCC1=NC=CC=N1 MSFVEEFXECBJPG-UHFFFAOYSA-N 0.000 description 1
• QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 1
• ZVJRJPHEWFGMAX-UHFFFAOYSA-N 2-[(methylideneamino)-[1-[(3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl)methyl]imidazol-2-yl]methylidene]pent-3-enenitrile Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C(N=C)=C(C=CC)C#N ZVJRJPHEWFGMAX-UHFFFAOYSA-N 0.000 description 1
• DXFPPOJKGNNLKF-UHFFFAOYSA-N 2-[1-[[8-(3-fluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl]methyl]imidazol-2-yl]pyridine-3-carbonitrile Chemical compound N1=CN2C=NN=C2C(CCCF)=C1CN1C=CN=C1C1=NC=CC=C1C#N DXFPPOJKGNNLKF-UHFFFAOYSA-N 0.000 description 1
• LOXROGHWAYYRSG-UHFFFAOYSA-N 2-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]acetaldehyde Chemical compound N1=CN2N=C(C)N=C2C(CC=O)=C1CN1C=CN=C1C1=NC=CC=C1F LOXROGHWAYYRSG-UHFFFAOYSA-N 0.000 description 1
• 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
• FWOHDAGPWDEWIB-UHFFFAOYSA-N 2-bromoethoxymethylbenzene Chemical compound BrCCOCC1=CC=CC=C1 FWOHDAGPWDEWIB-UHFFFAOYSA-N 0.000 description 1
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• DORHILWDHHOAIL-UHFFFAOYSA-N 3-bromo-2-(1h-imidazol-2-yl)pyridine Chemical compound BrC1=CC=CN=C1C1=NC=CN1 DORHILWDHHOAIL-UHFFFAOYSA-N 0.000 description 1
• HCOPIUVJCIZALB-UHFFFAOYSA-N 3-bromopyridine-2-carbonitrile Chemical compound BrC1=CC=CN=C1C#N HCOPIUVJCIZALB-UHFFFAOYSA-N 0.000 description 1
• CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• 125000005925 3-methylpentyloxy group Chemical group 0.000 description 1
• JTNRDIPRAWKORR-UHFFFAOYSA-N 4-(bromomethyl)-6-chloro-5-propylpyrimidine Chemical compound CCCC1=C(Cl)N=CN=C1CBr JTNRDIPRAWKORR-UHFFFAOYSA-N 0.000 description 1
• FANUNJNYFIVFCU-UHFFFAOYSA-N 4-azidopyrimidine Chemical compound [N-]=[N+]=NC1=CC=NC=N1 FANUNJNYFIVFCU-UHFFFAOYSA-N 0.000 description 1
• MKSGHLKYQCBBIQ-UHFFFAOYSA-N 4-chloro-6-(chloromethyl)-5-propylpyrimidine Chemical compound CCCC1=C(Cl)N=CN=C1CCl MKSGHLKYQCBBIQ-UHFFFAOYSA-N 0.000 description 1
• XWXPSQYSSKCHSM-UHFFFAOYSA-N 4-chloro-6-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-propylpyrimidine Chemical compound CCCC1=C(Cl)N=CN=C1CN1C(C=2C(=CC=CN=2)F)=NC=C1 XWXPSQYSSKCHSM-UHFFFAOYSA-N 0.000 description 1
• VYEBMLWGSMNCMJ-UHFFFAOYSA-N 4-chloro-6-methyl-5-propylpyrimidine Chemical compound CCCC1=C(C)N=CN=C1Cl VYEBMLWGSMNCMJ-UHFFFAOYSA-N 0.000 description 1
• DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical compound ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 description 1
• HTMGQIXFZMZZKD-UHFFFAOYSA-N 5,6,7,8-tetrahydroisoquinoline Chemical compound N1=CC=C2CCCCC2=C1 HTMGQIXFZMZZKD-UHFFFAOYSA-N 0.000 description 1
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
• XTRLIKXVRGWTKW-UHFFFAOYSA-N 6-chloropyridine-2-carbaldehyde Chemical compound ClC1=CC=CC(C=O)=N1 XTRLIKXVRGWTKW-UHFFFAOYSA-N 0.000 description 1
• UAJIFHDSCLQUON-UHFFFAOYSA-N 6-methyl-5-propyl-1h-pyrimidin-4-one Chemical compound CCCC1=C(C)NC=NC1=O UAJIFHDSCLQUON-UHFFFAOYSA-N 0.000 description 1
• MSAMDYNIRBHZAJ-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine-3-carbonitrile Chemical compound N1=CN2C(C#N)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F MSAMDYNIRBHZAJ-UHFFFAOYSA-N 0.000 description 1
• ZWKUIXONAUCDHB-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine-2-carboxamide Chemical compound N1=CN2C=C(C(N)=O)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 ZWKUIXONAUCDHB-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 235000006491 Acacia senegal Nutrition 0.000 description 1
• YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 1
• 102000009027 Albumins Human genes 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 238000010953 Ames test Methods 0.000 description 1
• 231100000039 Ames test Toxicity 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 206010002758 Anticipatory anxiety Diseases 0.000 description 1
• 101800004538 Bradykinin Proteins 0.000 description 1
• 102400000967 Bradykinin Human genes 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 206010007269 Carcinogenicity Diseases 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 108010062745 Chloride Channels Proteins 0.000 description 1
• 102000011045 Chloride Channels Human genes 0.000 description 1
• 102100031506 Complement C5 Human genes 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 102100021752 Corticoliberin Human genes 0.000 description 1
• 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 108010074922 Cytochrome P-450 CYP1A2 Proteins 0.000 description 1
• 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 description 1
• 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 description 1
• 108010001202 Cytochrome P-450 CYP2E1 Proteins 0.000 description 1
• 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 1
• 102100026533 Cytochrome P450 1A2 Human genes 0.000 description 1
• 102100036194 Cytochrome P450 2A6 Human genes 0.000 description 1
• 102100029358 Cytochrome P450 2C9 Human genes 0.000 description 1
• 102100021704 Cytochrome P450 2D6 Human genes 0.000 description 1
• 102100024889 Cytochrome P450 2E1 Human genes 0.000 description 1
• 102100039205 Cytochrome P450 3A4 Human genes 0.000 description 1
• 108010052832 Cytochromes Proteins 0.000 description 1
• 102000018832 Cytochromes Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
• 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 238000006088 Dimroth rearrangement reaction Methods 0.000 description 1
• 102000015554 Dopamine receptor Human genes 0.000 description 1
• 108050004812 Dopamine receptor Proteins 0.000 description 1
• 206010013887 Dysarthria Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 244000228957 Ferula foetida Species 0.000 description 1
• PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
• 206010019842 Hepatomegaly Diseases 0.000 description 1
• 101000875170 Homo sapiens Cytochrome P450 2A6 Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 208000000224 Night Terrors Diseases 0.000 description 1
• 206010029412 Nightmare Diseases 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 229910019213 POCl3 Inorganic materials 0.000 description 1
• LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102100033721 Pro-MCH Human genes 0.000 description 1
• 102100028427 Pro-neuropeptide Y Human genes 0.000 description 1
• 102000002067 Protein Subunits Human genes 0.000 description 1
• 108010001267 Protein Subunits Proteins 0.000 description 1
• 206010041010 Sleep terror Diseases 0.000 description 1
• 206010041250 Social phobia Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• 208000003028 Stuttering Diseases 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 102000003141 Tachykinin Human genes 0.000 description 1
• 241001582429 Tetracis Species 0.000 description 1
• 208000023655 Tic Diseases 0.000 description 1
• 208000008234 Tics Diseases 0.000 description 1
• 208000000323 Tourette Syndrome Diseases 0.000 description 1
• 208000016620 Tourette disease Diseases 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
• 241000269368 Xenopus laevis Species 0.000 description 1
• WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 230000037328 acute stress Effects 0.000 description 1
• 208000026345 acute stress disease Diseases 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 201000007930 alcohol dependence Diseases 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000001430 anti-depressive effect Effects 0.000 description 1
• 229940125681 anticonvulsant agent Drugs 0.000 description 1
• 239000001961 anticonvulsive agent Substances 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 239000002249 anxiolytic agent Substances 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 229940125717 barbiturate Drugs 0.000 description 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
• 210000004958 brain cell Anatomy 0.000 description 1
• 230000003925 brain function Effects 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• 125000005997 bromomethyl group Chemical group 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 231100000260 carcinogenicity Toxicity 0.000 description 1
• 230000007670 carcinogenicity Effects 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000006037 cell lysis Effects 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 231100000505 clastogenic Toxicity 0.000 description 1
• 230000003541 clastogenic effect Effects 0.000 description 1
• 230000002566 clonic effect Effects 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 230000007370 cognitive improvement Effects 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000024203 complement activation Effects 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940125851 compound 27 Drugs 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 210000005257 cortical tissue Anatomy 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 231100000263 cytotoxicity test Toxicity 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 230000003001 depressive effect Effects 0.000 description 1
• 238000004807 desolvation Methods 0.000 description 1
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
• 229960003529 diazepam Drugs 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• IRUNKQSGDBYUDC-UHFFFAOYSA-N diethoxymethyl acetate Chemical compound CCOC(OCC)OC(C)=O IRUNKQSGDBYUDC-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 229960003638 dopamine Drugs 0.000 description 1
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 230000036267 drug metabolism Effects 0.000 description 1
• 238000002565 electrocardiography Methods 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 238000011990 functional testing Methods 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 230000003400 hallucinatory effect Effects 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 230000002102 hyperpolarization Effects 0.000 description 1
• 239000003326 hypnotic agent Substances 0.000 description 1
• 230000000147 hypnotic effect Effects 0.000 description 1
• PQWQQQGKMHENOC-UHFFFAOYSA-N imidazo[1,2-c]pyrimidine Chemical class C1=NC=CC2=NC=CN21 PQWQQQGKMHENOC-UHFFFAOYSA-N 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229940125425 inverse agonist Drugs 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000003292 kidney cell Anatomy 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 238000000670 ligand binding assay Methods 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 208000024714 major depressive disease Diseases 0.000 description 1
• 210000005171 mammalian brain Anatomy 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000013507 mapping Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000010291 membrane polarization Effects 0.000 description 1
• 102000006240 membrane receptors Human genes 0.000 description 1
• 108020004084 membrane receptors Proteins 0.000 description 1
• 230000015654 memory Effects 0.000 description 1
• 230000009225 memory damage Effects 0.000 description 1
• 230000006993 memory improvement Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• KSSHPPPOAMTFQG-UHFFFAOYSA-N methyl 2-acetylpentanoate Chemical compound CCCC(C(C)=O)C(=O)OC KSSHPPPOAMTFQG-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000007758 minimum essential medium Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 230000036651 mood Effects 0.000 description 1
• 231100000219 mutagenic Toxicity 0.000 description 1
• 230000003505 mutagenic effect Effects 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• POFWRMVFWIJXHP-UHFFFAOYSA-N n-benzyl-9-(oxan-2-yl)purin-6-amine Chemical compound C=1C=CC=CC=1CNC(C=1N=C2)=NC=NC=1N2C1CCCCO1 POFWRMVFWIJXHP-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 description 1
• 208000019899 phobic disease Diseases 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 238000002600 positron emission tomography Methods 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000000216 proconvulsive effect Effects 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000005412 pyrazyl group Chemical group 0.000 description 1
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
• IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 description 1
• ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000006462 rearrangement reaction Methods 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 238000001525 receptor binding assay Methods 0.000 description 1
• 239000002469 receptor inverse agonist Substances 0.000 description 1
• 229940075993 receptor modulator Drugs 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 238000005096 rolling process Methods 0.000 description 1
• 238000009666 routine test Methods 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 238000003345 scintillation counting Methods 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229940125723 sedative agent Drugs 0.000 description 1
• 230000001624 sedative effect Effects 0.000 description 1
• 230000035807 sensation Effects 0.000 description 1
• 208000025874 separation anxiety disease Diseases 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 238000002603 single-photon emission computed tomography Methods 0.000 description 1
• 231100000188 sister chromatid exchange Toxicity 0.000 description 1
• 208000022925 sleep disturbance Diseases 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 235000011069 sorbitan monooleate Nutrition 0.000 description 1
• 239000001593 sorbitan monooleate Substances 0.000 description 1
• 229940035049 sorbitan monooleate Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 208000027765 speech disease Diseases 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 108060008037 tachykinin Proteins 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical group 0.000 description 1
• 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 239000003440 toxic substance Substances 0.000 description 1
• 231100000820 toxicity test Toxicity 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000006000 trichloroethyl group Chemical group 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 238000002211 ultraviolet spectrum Methods 0.000 description 1
• 238000005292 vacuum distillation Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 230000003936 working memory Effects 0.000 description 1
• AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 1